TY - JOUR

T1 - Calculation of Energy for RNA/RNA and DNA/RNA Duplex Formation by Molecular Dynamics Simulation

AU - Golyshev, V. M.

AU - Pyshnyi, D. V.

AU - Lomzov, A. A.

N1 - Funding Information: The work was supported by the Russian Foundation for Basic Research and the Government of the Novosibirsk region (grant no. 20-43-5430291) and funded budget project of The Program of Fundamental Scientific Research of State Academies of Sciences no. AAAA-A 17-117020210021-7. Publisher Copyright: © 2021, The Author(s).

PY - 2021/11

Y1 - 2021/11

N2 - The development of approaches for predictive calculation of hybridization properties of various nucleic acid (NA) derivatives is the basis for the rational design of the NA-based constructs. Modern advances in computer modeling methods provide the feasibility of these calculations. We have analyzed the possibility of calculating the energy of DNA/RNA and RNA/RNA duplex formation using representative sets of complexes (65 and 75 complexes, respectively). We used the classical molecular dynamics (MD) method, the MMPBSA or MMGBSA approaches to calculate the enthalpy (ΔH°) component, and the quasi-harmonic approximation (Q-Harm) or the normal mode analysis (NMA) methods to calculate the entropy (ΔS°) contribution to the Gibbs energy ($$\Delta G_{{37}}^{^\circ }$$) of the NA complex formation. We have found that the MMGBSA method in the analysis of the MD trajectory of only the NA duplex and the empirical linear approximation allow calculation of the enthalpy of formation of the DNA, RNA, and hybrid duplexes of various lengths and GC content with an accuracy of 8.6%. Within each type of complex, the combination of rather efficient MMGBSA and Q-Harm approaches being applied to the trajectory of only the bimolecular complex makes it possible to calculate the $$\Delta G_{{37}}^{^\circ }$$ of the duplex formation with an error value of 10%. The high accuracy of predictive calculation for different types of natural complexes (DNA/RNA, DNA/RNA, and RNA/RNA) indicates the possibility of extending the considered approach to analogs and derivatives of nucleic acids, which gives a fundamental opportunity in the future to perform rational design of new types of NA-targeted sequence-specific compounds.

AB - The development of approaches for predictive calculation of hybridization properties of various nucleic acid (NA) derivatives is the basis for the rational design of the NA-based constructs. Modern advances in computer modeling methods provide the feasibility of these calculations. We have analyzed the possibility of calculating the energy of DNA/RNA and RNA/RNA duplex formation using representative sets of complexes (65 and 75 complexes, respectively). We used the classical molecular dynamics (MD) method, the MMPBSA or MMGBSA approaches to calculate the enthalpy (ΔH°) component, and the quasi-harmonic approximation (Q-Harm) or the normal mode analysis (NMA) methods to calculate the entropy (ΔS°) contribution to the Gibbs energy ($$\Delta G_{{37}}^{^\circ }$$) of the NA complex formation. We have found that the MMGBSA method in the analysis of the MD trajectory of only the NA duplex and the empirical linear approximation allow calculation of the enthalpy of formation of the DNA, RNA, and hybrid duplexes of various lengths and GC content with an accuracy of 8.6%. Within each type of complex, the combination of rather efficient MMGBSA and Q-Harm approaches being applied to the trajectory of only the bimolecular complex makes it possible to calculate the $$\Delta G_{{37}}^{^\circ }$$ of the duplex formation with an error value of 10%. The high accuracy of predictive calculation for different types of natural complexes (DNA/RNA, DNA/RNA, and RNA/RNA) indicates the possibility of extending the considered approach to analogs and derivatives of nucleic acids, which gives a fundamental opportunity in the future to perform rational design of new types of NA-targeted sequence-specific compounds.

KW - DNA/RNA

KW - duplexes

KW - hybridization

KW - MMGBSA

KW - MMPBSA

KW - molecular dynamics

KW - oligonucleotides

KW - RNA/RNA

KW - thermal stability

UR - http://www.scopus.com/inward/record.url?scp=85121443615&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/b1c8a3a3-da61-3584-9354-321cddfe05b3/

U2 - 10.1134/S002689332105006X

DO - 10.1134/S002689332105006X

M3 - Article

AN - SCOPUS:85121443615

VL - 55

SP - 927

EP - 940

JO - Molecular Biology

JF - Molecular Biology

SN - 0026-8933

IS - 6

M1 - 13

ER -